DESCRIPTION (Adapted from the Principal investigator's Abstract): The purpose of this project is to study signal transduction and cell cycle progression using neurofibromin-deficient B lymphocytes generated by transferring Nf1-/-fetal liver cells into Rag1-/- mice. The identity of a specific 75-78kD protein, which comigrates with Btk, and which is specifically not phosphorylated on tyrosine residues in antigen receptor- stimulated neurofibromin-deficient B-cells will be determined. The ability of these cells to proliferate in response to antigen receptor crosslinking, CD40 ligation, and IL-4 will be examined. Reconstituted mice will be observed long-term for lymphoproliferation and responses to T- dependent and T-independent antigens will also be examined. Studies will be performed to examine whether neurofibromin plays a role in promoting specific tyrosine phosphorylation events, or whether it is a negative regulator of specific phosphotyrosyl phosphatases. Proteins that specifically associate with neurofibromin in B lymphocytes will be purified.